A Study of Nivolumab Safety and Pharmacokinetics in Patients With Severe Sepsis or Septic Shock.

April 19, 2019 updated by: Bristol-Myers Squibb

Randomized, Double-Blind, Parallel Group Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-936558 (Nivolumab) in Participants With Severe Sepsis or Septic Shock.

A study to evaluate the safety, tolerability and pharmacokinetics of Nivolumab in participants with severe sepsis or septic shock.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • UC Davis Medical Center
    • Colorado
      • Colorado Springs, Colorado, United States, 80909
        • Univ. Of Colorado Health
      • Denver, Colorado, United States, 80204
        • Denver Health Medical Center
    • Florida
      • Gainesville, Florida, United States, 32610
        • University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Pulmonary and Critical Care of Atlanta
    • Illinois
      • Peoria, Illinois, United States, 61637
        • OSF Saint Francis Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center (Bidmc)
      • Springfield, Massachusetts, United States, 01199
        • Baystate Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-5008
        • University of Michigan, Division of Acute Care Surgery
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261-2500
        • UPMC
    • Washington
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Men and women ages ≥ 18 years old
  • Documented or suspected infection
  • Severe sepsis or septic shock for at least 24 hours
  • Sepsis-induced immunosuppression
  • In Intensive Care Unit (ICU) with no plans to discharge in next 24 hours

Exclusion Criteria:

  • Previous episode of severe sepsis or septic shock with ICU admission during the current hospitalization
  • Autoimmune disease
  • Organ or bone marrow transplant
  • Cancer treatment in the past 6 weeks
  • Human immunodeficiency virus (HIV) infection and not on therapy prior to this episode of sepsis; hepatitis C virus(HCV) infection and still has virus (not cured); Chronic hepatitis B virus (HBV) infection and not on treatment

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Nivolumab 1
Dose 1
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
EXPERIMENTAL: Nivolumab 2
Dose 2
Biological: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Incidence Rates of Serious Adverse Events (SAEs), Adverse Events (AEs), Immune-mediated AEs, AEs Leading to Discontinuation, and Deaths
Time Frame: Screening, day -1, day 1 and subsequent days after, up to 90 days
Screening, day -1, day 1 and subsequent days after, up to 90 days
Composite of Vital Signs and Electrocardiogram (ECG)
Time Frame: Screening up to 90 days (Discharge)
Includes body temperature, respiratory rate, blood pressure and heart rate. Blood pressure and heart rate should be measured after the participant has been resting quietly for at least 5 minutes.
Screening up to 90 days (Discharge)
Peak Nivolumab Serum Concentration (Cmax)
Time Frame: Day 1 and subsequent days after, up to 90 days
Participants peak nivolumab serum concentration
Day 1 and subsequent days after, up to 90 days
Trough Nivolumab Serum Concentration (Cmin)
Time Frame: Day 1 and subsequent days after, up to 90 days
Participant trough nivolumab serum concentration
Day 1 and subsequent days after, up to 90 days
Average Nivolumab Serum Concentration (Cavg)
Time Frame: Day 1 and subsequent days after, up to 90 days
Participant average nivolumab serum concentration
Day 1 and subsequent days after, up to 90 days
Time of Maximum Observed Concentration (Tmax)
Time Frame: Day 1 and subsequent days after, up to 90 days
Participant observed time of maximum concentration
Day 1 and subsequent days after, up to 90 days
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration [AUC(0-T)]
Time Frame: Day 1 and subsequent days after, up to 90 days
Area under the serum concentration-time curve from time zero to time of last quantifiable concentration
Day 1 and subsequent days after, up to 90 days
Total Clearance (CLT)
Time Frame: Day 1 and subsequent days after, up to 90 days
Total clearance of serum concentration of nivolumab
Day 1 and subsequent days after, up to 90 days
Volume of Distribution (Vd)
Time Frame: Day 1 and subsequent days after, up to 90 days
Vlume of distribution of nivolumab serum concentration
Day 1 and subsequent days after, up to 90 days
Half-life (T1/2)
Time Frame: Day 1 and subsequent days after, up to 90 days
Half-Life of nivolumab derived from serum concentration
Day 1 and subsequent days after, up to 90 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Receptor Occupancy
Time Frame: Day 1 and up to day 90 (discharge)
Receptor occupancy on T cells at baseline and after study treatment administration at planned sampling time points
Day 1 and up to day 90 (discharge)
Number of Participants With Detectable Anti-nivolumab Antibodies
Time Frame: Baseline and subsequent days after, up to 90 days
Participant with positive anti-drug antibody detection
Baseline and subsequent days after, up to 90 days
Number of Participants With Any Detectable Anti-drug Antibodies
Time Frame: Baseline and subsequent days after, up to 90 days
Baseline and subsequent days after, up to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 7, 2016

Primary Completion (ACTUAL)

January 5, 2018

Study Completion (ACTUAL)

January 5, 2018

Study Registration Dates

First Submitted

November 8, 2016

First Submitted That Met QC Criteria

November 9, 2016

First Posted (ESTIMATE)

November 10, 2016

Study Record Updates

Last Update Posted (ACTUAL)

April 23, 2019

Last Update Submitted That Met QC Criteria

April 19, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA209-923

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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